Assessment of utility values and QALYs after primary PCI with DP-Xience and BP-Biomatrix stents.

BACKGROUND: Primary percutaneous coronary intervention (PPCI) is the recommended treatment in ST elevated myocardial infarction (STEMI). The determination of Quality of life (QoL) for various options of coronary revascularization is important for establishment of a comprehensive care plan. Studies of QoL in interventional cardiology are scarce. Our study has compared utility scores and quality adjusted life year (QALY) of 2nd and 3rd generation drug eluting stents (DES). METHODS: An observational cohort study was conducted to evaluate QoL and QALY using EQ-5D-5L questionnaire. Patients undergoing PPCI between July-Dec 2019 were evaluated after completion of one year of procedure. RESULTS: Total 334 patients were evaluated, study population consisted of a greater number of males (87.13%) than females. Mean utility value was more in 3rd G Biomatrix stents; 0.829 ± 0.11 than 2nd G Xience stents; 0.794 ± 0.11 (p < 0.05). Visual analogue scale (VAS) value was also high in 3rd G DES (81.84 ± 8.29) as compared to 2nd G DES (77.81 ± 9.01); p< 0.05. A significant association was found between utility scores/VAS and age, DM, HTN, Current smoking, family history and CAD diagnosis. There was a gain of 0.035 QALY with the use of Biomatrix DES. CONCLUSION: Health related quality of life (HRQOL) is a leading support in the decision making of therapeutic interventions. Our study has found that Biodegradable polymer (BP) Biomatrix DES are superior to the Durable polymer (DP) Xience DES having better QoL and QALY.

Formulation development and characterization of cefazolin nanoparticles-loaded cross-linked films of sodium alginate and pectin as wound dressings.

The present study focuses on the preparation of nanoparticles-loaded ionic cross-linked films for the topical delivery of cefazolin. The aim of the study was to prepare a dosage form which can provide local effect of cefazolin along with sustained delivery at the site of application. Cefazolin was loaded into chitosan nanoparticles to mask the burst release of the drug and they were optimized based on particle size, PDI, % EE and zeta potential. Finally, the prepared nanoparticles were loaded into the films comprising of sodium alginate and pectin which were then subjected to cross-linking via calcium chloride to improve the mechanical strength of the hydrogel films upon exposure to wound fluid. The films were assessed for physical and mechanical properties, swelling behavior, water transmission rate, mucoadhesion, FTIR, DSC, percent inhibition assay and in vitro release profile. Optimized formulation with Cefazolin nanoparticles in the size range of 227 nm and 0.5% CL films showed significantly better results (p < 0.05) as compared to the films with increased cross-linker concentration. Therefore, 0.5% CL films were considered more suitable for the treatment of infections when applied as wound dressing.

Formulation and in vitro evaluation of directly compressed controlled release tablets designed from the Co-precipitates.

Controlled release dosage forms provide sustained therapeutics effects for prolonged period of time and improve patient compliance. In present study, controlled release co-precipitates of Metoprolol Tartrate and Losartan Potassium were prepared by solvent evaporation method using polymers such as Eudragit RL 100 and Carbopol 974PNF and controlled release tablets were directly compressed into tablets. In-vitro dissolution of controlled release co-precipitates were performed by USP Method-II (paddle method) and tablets were evaluated by USP Method-I (rotating basket method) in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature was maintained constant at 37±1.0°C and the rotation speed of paddle and basket was kept constant at 100rpm. Drug release mechanisms were determined by applying Power Law kinetic model. The difference and similarity of dissolution profiles test formulations with reference standards were also determined by applying difference factor (f1) and similarity factor (f2). The results showed that the controlled release co-precipitates with polymer Eudragit RL 100 of both the drug extended the drug release rates for 10 hours and those having polymer Carbopol 974P NF extended the drug release rates for 12 hours. The controlled release tablets prepared from controlled release co-precipitates extended the drugs release up to 24 hours with both the polymers. The drug was released by all tests anomalous non fickian mechanism except F1 and F5 do not follow Power Law. The f1 and f2 values obtained were not in acceptable limits except F15 whose values were in acceptable limits. It is concluded from the present study that polymers (Eudragit RL 100 and Carbopol 974P NF) can be efficiently used in development of controlled release dosage forms having predictable kinetics.

Appraisal of phytochemical and in vitro biological attributes of an unexplored folklore: Rhus Punjabensis Stewart.

BACKGROUND: The role of plants for discovery of therapeutic potential accentuates the need to know their biological attributes. The present study aims to comprehend the biological attributes of Rhus punjabensis, an unexplored traditional medicinal plant. METHODS: Leaf and stem extracts of R. punjabensis prepared in 11 different organic solvents are evaluated for multimode antioxidant potential, total phenolic and flavonoid contents were determined through colorimetric assays, HPLC-DAD analysis was carried out for quantification of various polyphenols in extracts. Brine shrimp lethality, SRB and MTT assays were used to elucidate plant's cytotoxic and antileishmanial potentials. Disc diffusion assay was used to elucidate the protein kinase inhibitory, antibacterial and antifungal spectrum. RESULTS: Ethanol + ethyl acetate yielded maximum extract recovery from leaf (6.11 ± 1.09% w/w), total phenolic content (80.5 ± 2.18 µg GAE/mg extract) and reducing power potential (165.4 ± 2.29 µg AAE/mg extract). Maximum flavonoid content (30.50 ± 1.11 µg QE/mg extract) and highest DPPH based free radical scavenging activity (IC50 11.4 ± 2.07) was exhibited by the methanol + chloroform leaf extract. The methanol extract showed maximum total antioxidant capacity (74.5 ± 2.25 µg AAE/mg DW), protein kinase inhibitory (12.5 ± 1.10 bald phenotype at 100 µg/disc) and antifungal (MIC = 25 µg/disc against Aspergillus flavus) potential. Reverse phase HPLC-DAD based quantification reveals presence of gallic acid, apigenin, rutin and catechin in various extracts. Brine shrimp lethality assay demonstrated most extracts as highly cytotoxic (LC50 < 50 µg/mL) whereas chloroform extract of leaf demonstrated maximuminhibition against human leukemia cell line (IC50 7.80 ± 0.01 µg/mL). A significant activity against leishmanial promastigotes was demonstrated by n-hexane leaf extract (IC50 = 15.78 ± 0.15 µg/mL). A better antibacterial activity,by the extracts, against Gram positive strains as compared to Gram negative was observed. CONCLUSIONS: Results recommend multiple-solvent system as a critical factor to sumptuous the biological prospective of R. punjabensis and propose it to be a useful natural hub for the discovery of novel antioxidant, anticancer, antileishmanial and antimicrobial agents.

Isatis tinctoria mediated synthesis of amphotericin B-bound silver nanoparticles with enhanced photoinduced antileishmanial activity: A novel green approach.

After malaria, Leishmaniasis is the most prevalent infectious disease in terms of fatality and geographical distribution. The availability of a limited number of antileishmanial agents, emerging resistance to the available drugs, and the high cost of treatment complicate the treatment of leishmaniasis. To overcome these issues, critical research for new therapeutic agents with enhanced antileishmanial potential and low treatment cost is needed. In this contribution, we developed a green protocol to prepare biogenic silver nanoparticles (AgNPs) and amphotericin B-bound biogenic silver nanoparticles (AmB-AgNPs). Phytochemicals from the aqueous extract of Isatis tinctoria were used as reducing and capping agents to prepare silver nanoparticles. Amphotericin B was successfully adsorbed on the surface of biogenic silver nanoparticles. The prepared nanoparticles were characterized by various analytical techniques. UV-Visible spectroscopy was employed to detect the characteristic localized surface plasmon resonance peaks (LSPR) for the prepared nanoparticles. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) studies revealed the formation of spherical silver nanoparticles with an average particle size of 10-20nm. The cubic crystalline structure of the prepared nanoparticles was confirmed by X-ray diffraction (XRD) study. FTIR spectroscopic analysis revealed that plant polyphenolic compounds are mainly involved in metal reduction and capping. Under visible light irradiation, biogenic silver nanoparticles exhibited significant activity against Leishmania tropica with an IC50 value of 4.2µg/mL. The leishmanicidal activity of these nanoparticles was considerably enhanced by conjugation with amphotericin B (IC50=2.43µg/mL). In conclusion, the findings of this study reveal that adsorption of amphotericin B, an antileishmanial drug, to biogenic silver nanoparticles, could be a safe, more effective and economic alternative to the available antileishmanial strategies.

Formulation and in vitro evaluation of clotrimazole gel containing almond oil and tween 80 as penetration enhancer for topical application.

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermal and transdermal products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to develop Clotrimazole gel and to evaluate the effect of almond oil and tween 80 (in different concentrations), on the permeation of drug through rabbit skin in vitro. In order to investigate the effect of penetration enhancers used in this study on the permeation of Clotrimazole through sections of excised rabbit skin, Franz diffusion cell was employed. Sample solution was withdrawn at specific time interval up to 24 h. Significant difference in permeation among the eight formulations was seen in the study. The permeation profile of various formulations also showed that the added enhancers in individual batches affected the permeation of the drug. Drug permeation increased with increased concentration of Tween 80 and decreased concentration of almond oil. Furthermore, almond oil combined with tween 80 showed synergistic effect. The clotrimazole gels were successfully formulated and could be beneficial for topical use.

Effect of olive oil on transdermal penetration of flurbiprofen from topical gel as enhancer.

The present study was conducted to formulate and evaluate flurbiprofen transdermal gel. A standard calibration curve was constructed to obtain a regression line equation to be used for finding out the concentration of drug in samples. Olive oil was used as penetration enhancer and was added in different concentrations to some selected formulations to see its enhancement effect on in vitro drug release profiles. The prepared gels were evaluated for several physico-chemical parameters to justify their suitability for topical use. The in vitro drug release studies were carried out by using Franz cell diffusion apparatus across both synthetic membrane and excised albino rabbit skin. In order to investigate the drug release mechanism a kinetic approach was made by employing Korsmeyer kinetic model to the in vitro drug release profiles of flurbiprofen. The flurbiprofen topical gels were successfully prepared and could be beneficial for topical use.

Development of a novel ketoprofen transdermal patch: effect of almond oil as penetration enhancers on in-vitro and ex-vivo penetration of ketoprofen through rabbit skin.

The aim of the study was to formulate and evaluate topically applied ketoprofen gels and patches and to see the effect of naturally occurring almond oil as penetration enhancer on the penetration of ketoprofen through artificial membrane/rabbit skin. Prior to ketoprofen gel and patch formulation, the particle size and particle size determination of ketoprofen was analyzed by Particle size analyzer (Horiba LA300). Ketoprofen gels and patches were formulated and almond oil was added in several concentrations i.e. 0.5%, 1%, 1.5%, 2%, 2.5% and 3%. The formulated gels were evaluated by several parameters like pH, spreadibility, consistency, homogeneity, skin irritation and drug content determination. In vitro drug permeation studies from transdermal gels and patches were carried out across artificial membrane and rabbit skin by using Franz Cell Apparatus (PermeGear, USA). Kinetics model was employed to the release patterns of ketoprofen from gel and patches in order to investigate the drug transport mechanism. The cumulative amount of drug penetrated from different formulations was statistically evaluated by using One-way analysis of variance (ANOVA). Stability study was performed for various batches of ketoprofen transdermal gel. Almond oil as penetration enhancer in various concentrations significantly enhances the penetration of drug from transdermal gels and patch across synthetic membrane/rabbit skin but was most significant when used in 3% concentration.

Preparation and evaluation of 5, 9-dimethyl-2-cyclopropyl-2-decanol as a penetration enhancer for drugs through rat skin.

In the present study a new alcohol derivative of tetrahydrogeraniol (THG), an acyclic monoterpene, has been prepared by using Grignard reagent and methyl cyclopropyl ketone. Penetration enhancing effects of THG and the synthesized derivative 5,9-dimethyl-2-cyclopropyl-2-decanol (DICNOL) on the transdermal penetration of 5-fluorouracil (5-FU) and tramadol hydrochloride (tramadol HCl) across the excised rat skin were studied by an in vitro permeation technique using Franz diffusion cells. Azone was used as standard enhancer for comparison. DICNOL and THG significantly enhanced 5-FU and tramadol HCl penetration through rat skin compared with the control. DICNOL enhanced the permeability of 5-FU and tramadol HCl across full thickness skin by about 11 and 20 fold, respectively. Increased partition coefficient and diffusion coefficient values were obtained by these enhancers. The results suggest that the amount of DICNOL in the skin, especially in the stratum corneum, may be related to its penetration enhancing effects.

Novel acylated steroidal glycosides from Caralluma tuberculata induce caspase-dependent apoptosis in cancer cells.

AIM OF THE STUDY: Pregnane glycosides are potent cytotoxic agents which may represent new leads in the development of anti-tumour drugs, particularly in the treatment of breast cancer, because of the structural similarity to estrogenic agonists. Caralluma species are natural sources of a wide variety of pregnane glycosides. The aim of the study was to isolate, using an activity-guided fractionation approach, novel pregnane glycosides for testing on breast cancer and other tumour lines. MATERIALS AND METHODS: The effect of crude extracts, specific organic fractions and isolated compounds from Caralluma tuberculata was tested on the growth and viability of MCF-7 estrogen-dependent, and MDA-MB-468 estrogen-independent breast cancer cells, Caco-2 human colonic cells, HUVECs and U937 cells. Neutral red uptake and MTT assays were used. Apoptosis was detected by Western blot of poly-(ADP ribose) polymerase (PARP) as were other markers of nuclear fragmentation (DNA ladder assay, staining of cells with nuclear dye DAPI). The involvement of caspases was investigated using the pan-caspase inhibitor Z-VAD-FMK. RESULTS: The ethyl acetate fraction of Caralluma tuberculata was found to be the most potent anti-proliferative fraction against all three cancer cell lines. Two novel steroidal glycosides were isolated from the active fraction after a series of chromatographic experiments. The structure of the isolated compounds was elucidated solely based on 2D-NMR (HMBC, HETCOR, DQF-COSY) and MS spectral analysis as compound 1: 12-O-benzoyl-20-O-acetyl-3ß,12ß,14ß,20ß-tetrahydroxy-pregnan-3-ylO-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranosyl-(1 → 4)-3-methoxy-ß-D-ribopyranoside, and as compound 2: 7-O-acetyl-12-O-benzoyl-3ß,7ß,12ß,14ß-tetrahydroxy-17ß-(3-methylbutyl-O-acetyl-1-yl)-androstan-3-ylO-ß-D-glucopyranosyl-(1 → 4)-6-deoxy-ß-D-allopyranosyl-(1 → 4)-ß-D-cymaropyranosyl-(1 → 4)-ß-D-cymapyranosyl-(1→ 4)-ß-D-cymaropyranoside. Compound 1 (pregnane glycoside) and compound 2 (androstan glycoside) induced apoptosis at <25 µM after 48 h as assessed by cell shrinkage, PARP cleavage, DNA fragmentation, and reversal with the caspase inhibitor. CONCLUSIONS: Two novel steroid glycosides isolated from Caralluma tuberculata possess moderate, micromolar cytotoxic activity on breast cancer and other cells in vitro, which may indicate a source of activity in vivo of interest to future drug design.

In vitro antifungal activity of Rhazya stricta.

Rhazya stricta is a small glabrous shrub, widely distributed throughout Western Asia from Yemen to Arabia, to the North West Province of India and abundantly found in various regions of Pakistan. Larvicidal and antifungal studies of polar and non polar aerial parts extracts of Rhazya stricta were performed using brine shrimps larvae for larvicidal study and for antifungal study microorganisms, Trichophyton longifusis, Aspergillus flavus, Candida albicans, Microsporum canis and Fusarium solani were used respectively. The methanol fraction showed significant cytotoxicity with LC50 17.809 microg/ml, having mortality rate 73.33% at highest dose. While pet-ether, chloroform and carbon tetrachloride possessed moderate to low cytotoxicity with their LC50 values 49.077 microg/ml, 95.859 microg/ml and 80.489 microg/ml respectively, ethyl acetate fraction showed no cytotoxicity. Results of antifungal studies showed that fractionated samples of methanol and chloroform possessed significant antifungal activities against, Trichophyton longifusis, Aspergillus flavus, Candida albicans and Fusarium solani respectively. Due to these promising results, further in vivo studies over R. stricta must be conducted.

Fermentative production of L-lysine: fungal fermentation and mutagenesis-II: a review.

Lysine has been recognized as one of the most deficient essential amino acids. It is an economically important food and feed supplement. It has also got various pharmaceutical applications in the formulation of diets with balanced amino acid concentration and in amino acid infusions. Chemical, enzymatic and fermentation processes have been used to synthesize lysine. The objective of this review is to outline the research work of various scientists which provide important and beneficial information regarding the production of lysine through fungal fermentation and mutagenesis. Moreover, methods to improve the total yield and quality of lysine are also presented.